bims-aditis 2022-05-22 papers

Issue of 2022–05–22
four papers selected by
Matthew C. Sinton, University of Glasgow

Med (N Y). 2022 May 13. pii: S2666-6340(22)00172-6. [Epub ahead of print]3(5): 276-278

Can we target obesity using a single-cell atlas of adipose tissue?

Adipose tissue is a multicellular tissue with depot-dependent functions including safe energy storage and release, immune defense, thermogenesis, and organ padding. Emont et al. zoom in on white adipose tissue at a single-cell resolution and provide an extensive resource for future insights in how to target obesity.1.

DOI: https://doi.org/10.1016/j.medj.2022.04.006

Front Immunol. 2022 ;13 835711

T Lymphocyte Exhaustion During Human and Experimental Visceral Leishmaniasis.

Juliana C Costa-Madeira, Gabrielly B Trindade, Paulo H P Almeida, João S Silva, Vanessa Carregaro.

A key point of immunity against protozoan Leishmania parasites is the development of an optimal T cell response, which includes a low apoptotic rate, high proliferative activity and polyfunctionality. During acute infection, antigen-specific T cells recognize the pathogen resulting in pathogen control but not elimination, promoting the development and the maintenance of a population of circulating effector cells that mount rapid response quickly after re-exposure to the parasite. However, in the case of visceral disease, the functionality of specific T cells is lost during chronic infection, resulting in inferior effector functions, poor response to specific restimulation, and suboptimal homeostatic proliferation, a term referred to as T cell exhaustion. Multiple factors, including parasite load, infection duration and host immunity, affect T lymphocyte exhaustion. These factors contribute to antigen persistence by promoting inhibitory receptor expression and sustained production of soluble mediators, influencing suppressive cell function and the release of endogenous molecules into chronically inflamed tissue. Together, these signals encourage several changes, reprogramming cells into a quiescent state, which reflects disease progression to more severe forms, and development of acquired resistance to conventional drugs to treat the disease. These points are discussed in this review.

Keywords: T cell exhaustion; Th subsets; inflammation; inhibitory receptor; visceral leishmanaisis

DOI: https://doi.org/10.3389/fimmu.2022.835711

Front Immunol. 2022 ;13 858051

The Metabolic Basis of ILC Plasticity.

Abigaelle Pelletier, Christian Stockmann.

Innate Lymphoid Cells (ILCs) are the innate counterpart of adaptive lymphoid T cells. They are key players in the regulation of tissues homeostasis and early inflammatory host responses. ILCs are divided into three groups, and further subdivided into five subsets, that are characterised by distinct transcription factors, surface markers and their cytokine expression profiles. Group 1 ILCs, including natural killer (NK) cells and non-NK cell ILC1s, express T-bet and produce IFN-γ. Group 2 ILCs depend on GATA3 and produce IL-4, IL-5 and IL-13. Group 3 ILCs, composed of ILC3s and Lymphoid Tissue Inducer (LTi) cells, express RORγt and produce IL-17 and IL-22. Even though, the phenotype of each subset is well defined, environmental signals can trigger the interconversion of phenotypes and the plasticity of ILCs, in both mice and humans. Several extrinsic and intrinsic drivers of ILC plasticity have been described. However, the changes in cellular metabolism that underlie ILC plasticity remain largely unexplored. Given that metabolic changes critically affect fate and effector function of several immune cell types, we, here, review recent findings on ILC metabolism and discuss the implications for ILC plasticity.

Keywords: Innate Lymphoid Cells (ILCs); OxPhos; cytokines; glycolysis; metabolism; plasticity

DOI: https://doi.org/10.3389/fimmu.2022.858051

FASEB J. 2022 Jun;36(6): e22346

Lamina propria interleukin 17 A aggravates natural killer T-cell activation in autoimmune hepatitis.

Jianing Chen, Xuehui Li, Ping Zeng, Xujun Zhang, Kefan Bi, Chenhong Lin, Jingjing Jiang, Hongyan Diao.

Autoimmune hepatitis is an interface hepatitis characterized by the progressive destruction of the liver parenchyma, the cause of which is still obscure. Interleukin (IL)-17A is a major driver of autoimmunity, which can be produced by innate immune cells against several intracellular pathogens. Here, we investigated the involvement of IL-17A in a mice model of immune-mediated hepatitis with the intestine exposed to Salmonella typhimurium. Our results showed more severe Concanavalin (Con) A-induced liver injury and gut microbiome dysbiosis when the mice were treated with a gavage of S. typhimurium. Then, the natural killer (NK) T cells were overactivated by the accumulated IL-17A in the liver in the Con A and S. typhimurium administration group. IL-17A could activate NKT cells by inducing CD178 expression via IL-4/STAT6 signaling. Furthermore, via the portal tract, the laminae propria mucosal-associated invariant T (MAIT)-cell-derived IL-17A could be the original driver of NKT cell overactivation in intragastric administration of S. typhimurium and Con A injection. In IL-17A-deficient mice, Con A-induced liver injury and NKT cell activation were alleviated. However, when AAV-sh-mIL-17a was used to specifically knock down IL-17A in liver, it seemed that hepatic IL-17a knock down did not significantly influence the liver injury. Our results suggested that, under Con A-induction, laminae propria MAIT-derived IL-17A activated hepatic NKT, and this axis could be a therapeutic target in autoimmune liver disease.

Keywords: autoimmune hepatitis; interleukin 17 A; lamina propria; natural killer T cells

DOI: https://doi.org/10.1096/fj.202101734RRR